14 June 2018 : Laboratory Research
Cervical Cancer Cell Growth, Drug Resistance, and Epithelial-Mesenchymal Transition Are Suppressed by γ-Secretase Inhibitor RO4929097
Lu Wang1ABE, Guo Dai2ABE, Jian Yang2G, Wanrong Wu1CDF, Wei Zhang1A*DOI: 10.12659/MSM.909452
Med Sci Monit 2018; 24: LBR4046-4053
Abstract
BACKGROUND: The Notch signaling pathway has been reported to play a pivotal role in tumorigenesis. Emerging evidence has demonstrated that the Notch signaling pathway regulates several cellular processes. The present study investigated the effect of the Notch signaling pathway on cell growth, invasiveness, and drug resistance, as well as epithelial-mesenchymal transition (EMT), of cervical cancer cells.
MATERIAL AND METHODS: We used quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis to measure the expression level of Notch2. CCK-8, clonality, wound healing, and Transwell assays were used to evaluate the effect of γ-secretase inhibitor (GSI) RO4929097 on cervical cancer cell lines HeLa and Caski. To explore the role of the Notch signaling pathway in EMT, the epithelial and mesenchymal markers were detected by qRT-PCR and Western blot after cervical cancer cell lines were treated with GSI RO4929097.
RESULTS: The expression of Notch2 was found to increase in cervical cancer cell lines compared with the normal immortalized human cervical epithelial cells. GSI RO4929097 was confirmed to inhibit the Notch signaling pathway and impaired the proliferation, drug resistance, migration, and invasion abilities of cervical cancer cells. The protein expression levels of the mesenchymal biomarkers Snail, Twist, and neural cadherin (N-cadherin) decreased; however, the expression of the epithelial biomarker epithelial cadherin (E-cadherin) increased in the cervical cancer cells treated with GSI RO4929097.
CONCLUSIONS: Notch signaling pathway plays an important role in the development and progression of cervical cancer. Blockade of the Notch pathway using GSI RO4929097 inhibited cell growth and reduced chemoresistance, invasion, metastasis, and EMT in cervical cancer cells.
Keywords: Epithelial-mesenchymal transition, Receptors, Notch
Editorial
01 May 2022 : Editorial
Editorial: Cardiovascular Complications at One Year After SARS-CoV-2 Infection are Independent of Underlying Cardiovascular Risk Factors or Severity of COVID-19DOI: 10.12659/MSM.937048
Med Sci Monit 2022; 28:e937048
SARS-CoV-2/COVID-19
24 May 2022 : Clinical Research
Screening for SARS-CoV-2 Infection in Students at the Medical University of Warsaw, Poland Between November...Med Sci Monit In Press; DOI: 10.12659/MSM.936962
04 May 2022 : Clinical Research
Effects of Wearing Face Masks on Exercise Capacity and Ventilatory Anaerobic Threshold in Healthy Subjects ...Med Sci Monit In Press; DOI: 10.12659/MSM.936069
22 April 2022 : Clinical Research
Factors Associated with Falls During Hospitalization for Coronavirus Disease 2019 (COVID-19)Med Sci Monit In Press; DOI: 10.12659/MSM.936547
25 May 2022 : Meta-Analysis
Effect of the COVID-19 Pandemic on Serum Vitamin D Levels in People Under Age 18 Years: A Systematic Review...Med Sci Monit 2022; 28:e935823
In Press
25 May 2022 : Review article
Narrative Review of the Mechanism of Hip Prosthesis Dislocation and Methods to Reduce the Risk of DislocationMed Sci Monit In Press; DOI: 10.12659/MSM.935665
24 May 2022 : Clinical Research
Remimazolam Tosilate Sedation with Adjuvant Sufentanil in Chinese Patients with Liver Cirrhosis Undergoing ...Med Sci Monit In Press; DOI: 10.12659/MSM.936580
24 May 2022 : Clinical Research
Screening for SARS-CoV-2 Infection in Students at the Medical University of Warsaw, Poland Between November...Med Sci Monit In Press; DOI: 10.12659/MSM.936962
23 May 2022 : Clinical Research
Fully Automatic Knee Joint Segmentation and Quantitative Analysis for Osteoarthritis from Magnetic Resonanc...Med Sci Monit In Press; DOI: 10.12659/MSM.936733
Most Viewed Current Articles
30 Dec 2021 : Clinical Research
Retrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...DOI :10.12659/MSM.935379
Med Sci Monit 2021; 27:e935379
08 Mar 2022 : Review article
A Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...DOI :10.12659/MSM.936292
Med Sci Monit 2022; 28:e936292
01 Nov 2020 : Review article
Long-Term Respiratory and Neurological Sequelae of COVID-19DOI :10.12659/MSM.928996
Med Sci Monit 2020; 26:e928996
01 Jan 2022 : Editorial
Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...DOI :10.12659/MSM.935952
Med Sci Monit 2022; 28:e935952